The PI has recently found increased binding of alpha-2 adrenoceptors (especially in the high affinity site) in platelets of women with dysphoric PMC. That increase was similar to changes in alpha-2 adrenoceptor binding in platelets of patients with major depressive disorder and highly correlated with severity of dysphoric symptoms. The proposed project is aimed at confirmation of that possible biological marker and elucidation of its association with baseline levels of gonadal hormones, mood, and behavior, as well as its changes during symptomatic and asymptomatic phases of the menstrual cycle. The role of the hypothalamo-pituitary-gonadal system will be further clarified by studies of alpha-2 receptor binding in postmenopausal women before and during estrogen replacement therapy. Alpha-2 adrenoceptor binding will be studied in 60 women of reproductive age who seek treatment for premenstrual dysphoric syndromes, as well as 20 post-menopausal women who will get estrogen replacement therapy, and two control groups: 20 healthy women who do not have premenstrual mood and behavioral changes but have physical changes, and 20 women who have no PMC. Women whose PMC will warrant treatment will repeat the tests following suppression of ovulation and fluctuations of gonadal hormones with 3 treatment modalities creating: a) low levels of gonadal hormones; b) higher levels of estrogen, and c) three different levels of progesterone.. The studies should result in a suggestion of the first testable biological marker for dysphoric PMC and should shed light on the influence of gonadal hormones on an adrenoceptor that might be involved in hormonally related dysphoric symptoms formation. If menstrually related, symptom related, and estrogen related alpha-2 binding changes are found, they might have implications for the design of future treatment approaches.